hong kong college of cardiology asm 2019 is there still a … cardiology...aspirin in secondary...
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Hong Kong College of Cardiology ASM 2019
Dr Tam Frankie CC 譚礎璋醫生 Division of Cardiology, Medicine
Queen Mary Hospital, University of Hong Kong
Is there still a role for aspirin in primary prevention?
Rationale of using Aspirin in CAD
Meadows TA et al Circ Res. 2007;100:1261-1275.
Aspirin inhibits platelets, reduces chance of thrombosis
Atherothrombosis
Anti-platelet and bleeding
As with all anti-platelet agents, reducing ischemia means
increasing bleeding risks
Art of balance
Ischemia
VS
Bleeding
Using Aspirin: benefit vs risk
Acute phase of event
Eg MI, stroke
Post event
Eg post MI, PCI, CABG
Evidence of atherosclerosis
Eg +ve CTA, mild CAD, carotid IMT
High risk of CVD
Eg DM, high ASCVD score
Risk of death
Secondary prevention
Primary prevention
‘1.5’ prevention
Aspirin in secondary prevention
ISIS2 Collaborative Group, Lancet 1988; II:349360.
Aspirin and streptokinase superior in
acute STEMI Aspirin beneficial in NSTE-ACS
Aspirin’s role undeniable in acute event
Antiplatelet Trialists’ Collaboration
ATC. BMJ 1994
Aspirin and Primary prevention
Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med. 1989
44% reduction in risk of a first MI,
p<0.001
Reduction in the risk of MI was
apparent only among those >50
years
No benefit on all cause mortality,
CV death and stroke
Aspirin and Primary prevention
Ridker PM, et al. N Engl J Med. 2005
Aspirin and Primary prevention
Ridker PM, et al. N Engl J Med. 2005
Aspirin and Primary prevention
Berger JS. Am Heart J 2011
Fatal/non-fatal MI
All cause mortality
CV death Meta-analysis:
‘Aspirin prevent MI’
Heterogenous study results
Most benefit derived from Physican
Health Study
Circulation. 2015; EHJ 2012
Class IIa
Class IIb
What does FDA say?
Aspirin and Primary prevention in 2019
Bleeding CV event
BALANCING RISK
Traditional CV risk factors
ASCVD Risk scores
DM
Bleeding risk factors
Risk scores
History of bleeding
Alternative treatment for CVD prevention
Eg statins, PCSK9 inh, SGLT-2 inhibitors, GLP-1
Alternative treatment to reduce bleeding risk
Eg PPI, HP eradication, endoscopic therapies
ARRIVE study
Lancet 2018
ARRIVE study: Study Design
• Male ≥55, 2/more CV risk factors; Female ≥60, 3/more CV risk factors
• Calculated cardiovascular risk (10-year risk of CHD of 10–20%)
• No Diabetes
• No history of vascular event
• No history of serious bleeding
Placebo N=6,276
Cartia 100mg QD N=6,270
Randomized, double-blinded,
placebo controlled
Primary endpoint:
Composite outcome consisting of time to first occurrence of confirmed
myocardial infarction, stroke, cardiovascular death, unstable angina, or
transient ischaemic attack
Median FU: 60 months
Primary prevention in high CV risk
ARRIVE study: Study Population
Actual event rate lower than expected (calculated)
Reflecting the effective contemporary CV medications
Primary prevention in high CV risk
ARRIVE study: Efficacy Outcome
Primary prevention in high CV risk
ARRIVE study: Safety Outcome
Primary prevention in high CV risk
ARRIVE study: Efficacy Outcome
Primary prevention in high CV risk
ARRIVE study: Efficacy Outcome
Per-Protocol analysis (N=7,702): only select subjects
with reasonably good drug compliance
Primary prevention in high CV risk
ARRIVE study: Conclusions
• With contemporary treatment, actual CV event rate seemed to decrease
• It is difficult to conduct primary prevention trials as patient compliance is fair in long run
• Aspirin seemed can reduce risk of MI if compliance is good, with increased risk of GI bleeding
Primary prevention in high CV risk
ASPREE study
NEJM 2018
ASPREE study: Study Design
• Age ≥70
• No history of cardiovascular, cerebrovascular disease
• No history of chronic illness which limit life expectancy
• No history of serious bleeding
Placebo N=9,589
Cartia 100mg QD N=9,525
Randomized, double-blinded,
placebo controlled
Primary endpoint: survival free from dementia or persistent physical disability
Key secondary endpoints: major hemorrhage and cardiovascular disease (defined as fatal
CHD, nonfatal MI, fatal or nonfatal stroke, or hospitalization for heart failure)
Median FU: 4.7 years
Primary prevention in Elderly
ASPREE study: Study population
~10% DM
Primary prevention in Elderly
ASPREE study: Efficacy Outcome
No significant benefit in CV event
Primary prevention in Elderly
ASPREE study: Safety Outcome
Increased risk
of major
bleeding
Primary prevention in Elderly
JPPP study
JAMA 2014
JPPP study: Study Design
• Age 60-85
• Hypertension OR hyperlipidemia OR DM
• No history of atherosclerosis, cardiovascular, cerebrovascular disease
• No history of serious bleeding
NO aspirin N=7,244
Cartia 100mg QD N=7,220
Randomized, open label
Primary endpoint: composite of death from cardiovascular causes (myocardial infarction,
stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic,
including undefined cerebrovascular events), and nonfatal myocardial infarction
Median FU: 5.02 years
Primary prevention in high CV risk
JPPP study: Study population
~30% DM
Primary prevention in high CV risk
JPPP study: Efficacy and safety outcome
No difference in primary endpoint
Reduction in non-fatal MI
Increase major bleeding
Primary prevention in high CV risk
JPPP study: Study population
Primary prevention in high CV risk
ASCEND study
NEJM 2018
ASCEND study: Study Design
• Age ≥40
• Diabetes Mellitus
• No history of cardiovascular disease
Placebo N=7,740
Cartia 100mg QD N=7,740
Randomized, double-blinded,
placebo controlled
Primary endpoint: first Serious Vascular Event (SVE),
which was defined as a composite of nonfatal myocardial infarction, nonfatal stroke or transient
ischemic attack, or death from any vascular cause.
Primary safety endpoint: first occurrence of any major bleeding event
Median FU: 7.4 years
Primary prevention in DM
ASCEND study: Study Population
Primary prevention in DM
ASCEND study: Efficacy outcome
Primary prevention in DM
ASCEND study: Efficacy outcome
Primary prevention in DM
ASCEND study: Safety outcome
Primary prevention in DM
ASCEND study: Risk benefit ratio
No significant difference
in risk-benefit ratio in
different subgroup
Primary prevention in DM
Meta-analysis in 2019
Zheng et al. JAMA. 2019;321(3):277-287
13 trials randomizing 164,225 participants with 1,050,511 participant-years of follow-up
Probably reduces CV event
Increases major bleeding
Meta-analysis in 2019
Zheng et al. JAMA. 2019;321(3):277-287
Similar outcome across
low OR high CV risk
Increase risk of
bleeding
Meta-analysis in 2019
Zheng et al. JAMA. 2019;321(3):277-287
Meta-analysis in 2019
Huang et al. JAMA. 2019
13 trials; 134,446 participants
Increases risk of ICH
Intracranial hemorrhage
Huang et al. JAMA. 2019
Intracranial
hemorrhage
Asians at higher risk
Meta-analysis in 2019
Stable atherosclerosis (‘1.5 prevention’)
Mild CAD on CTA
Mild CAD on CORO
Stable angina
Carotid IMT, mild carotid stenosis
Mild peripheral vascular disease (PVD)
Aspirin for asymptomatic atherosclerosis study
N=3,350, age 50-75
No history of MI or stroke or taking
Aspirin
ABI≤0.95
(PVD, asymptomatic atherosclerosis) Fowkes et al. JAMA. 2010
Stable atherosclerosis (‘1.5 prevention’)
Stable atherosclerosis (‘1.5 prevention’)
DM patients
No MI/stroke
Documented CAD Details pending
Aspirin + Ticagrelor
Vs
Aspirin
Post PCI vs CABG vs just
atherosclerosis
N=19,271
Acute phase of event
Eg MI, stroke
Post event
Eg post MI, PCI,
CABG
Stable atherosclerosis
High CV risk, DM
Aspirin indicated
Need to discuss with patients benefit and
risk of Aspirin
Benefit: probably reduces chance of MI
Risk: risk of bleeding (particularly GIB)
Aspirin if no C/I or low risk of bleeding (also depends on extent of atherosclerosis)
In the contemporary practice of
alternative treatment Eg Statins, PCSK9
SGLT-2 inh, GLP-1 for DM
Aspirin in prevention of CV event
Practical considerations
Hong Kong College of Cardiology ASM 2019
Dr Tam Frankie CC 譚礎璋醫生 Division of Cardiology, Medicine
Queen Mary Hospital, University of Hong Kong
Thank you